The objective of this research is to quantitate the development and characterize the mechanisms of chemical communication between cultured cerebellar neurons. Synaptic development in culture is an expression of genetic programming and quantitative morphometric methods will be used to assay for the time course and extent of synaptic development. Chemicals which are known to cause deficits in brain growth will be assayed for their ability to interfere with synaptic development in culture. The electrophysiological experiments are designed to elucidate the modes of synaptic activation in culture and will provide conclusive evidence of functional synapses in culture. Assays will then be conducted to identify the neurotransmitters present at the synapses. Other neuroactive drugs, such as LSD and amphetamines, will be assayed for their effect on synaptic transmission. The experimental procedure will involve assaying changes in patterns of postsynaptic electrocal activity during simultaneous electrical activation of the synapses and iontophoretic drug application. Histochemical assays of cyclic AMP and cyclic GMP will be performed to localize the cellular sites of rises in these chemicals seen following stimulation of the cerebellum with certain neurotransmitters.